Nature Sub-Journal: Single-base editor helps treat liver disease...

The programmable CRISPR-Cas nuclease achieves genome editing by breaking double-stranded DNA at the target location, but it is very inefficient in cells after mitosis.

For the clinical application of base editing, its main limitation lies in the generation of potential non-target mutations.

On May 19, 2021, Gerald Schwank of the Swiss Federal Institute of Technology Zurich and the team of Sean C.

PCSK9, mainly expressed in the liver, is a negative regulator of LDL receptors.

In vivo adenine base editing of Pcsk9 gene in mouse liver

Subsequently, the researchers explored non-target mutations caused by long-term ABE expression, and evaluated non-target mutations in DNA and RNA at the molecular level.

Pcsk9's in vivo adenine base editing does not induce a large number of non-target mutations in DNA

Finally, in order to further evaluate the feasibility of ABE in clinically relevant large animal models, the author edited PCSK9 in adult cynomolgus monkeys (cynomolgus monkeys).

In vivo adenine base editing of the PCSK9 locus in the liver of rhesus monkeys

In summary, this article studies the effectiveness and safety of ABEs in the liver of mice and cynomolgus monkeys in reducing blood low-density lipoprotein (LDL) levels.

The contents of plasma PCSK9 and LDL decreased steadily by 95% and 58% in mice, and decreased by 32% and 14% in rhesus monkeys.

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